CN1839837A - Nicorandil freeze-drying powder preparation method - Google Patents
Nicorandil freeze-drying powder preparation method Download PDFInfo
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- CN1839837A CN1839837A CN 200610041778 CN200610041778A CN1839837A CN 1839837 A CN1839837 A CN 1839837A CN 200610041778 CN200610041778 CN 200610041778 CN 200610041778 A CN200610041778 A CN 200610041778A CN 1839837 A CN1839837 A CN 1839837A
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- nicorandil
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- drying powder
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Abstract
The invention discloses a process for preparing Nicorandil freeze-dried powder, which consists of charging 0.1-50.0 wt% of Nicorandil into water for injection, dissolving excipient simultaneously, degerming and filtering, loading, and finally freeze drying.
Description
Technical field
The present invention relates to a kind of injection preparation method of medicine, the preparation method of nicorandil freeze-drying powder particularly, this method uses the amino acids material to be auxiliary shape agent, adopt Freeze Drying Technique to prepare the lyophilized powder of nicorandil, but intravenous injection is used, avoid nicorandil in water, to be degraded to the material of other toxic side effect, guaranteed the safety of patient's medication.This product solubility is better, directly adds dissolving backs such as sterilized water for injection, normal saline, glucose injection when using clinically and uses.
Background technology
Nicorandil has another name called Nicorandil, Nicorandil, belongs to nitrate compound, is the only treatment coronary heart disease with double action mechanism, anginal medicine in the cardiovascular system medicine that goes on the market at present.Its existing nitrate esters medicine coronary artery dilator blood vessel, the persistence coronary blood flow increasing suppresses the effect of coronary vasospasm, can stop the free of intracellular calcium again, increases the permeability of cell membrane to potassium ion.In addition, it also has anticoagulant, prevents thrombotic effect.
Because nicorandil is very easily degraded in aqueous solution, produces objectionable impurities, therefore nicorandil directly should not be made injection, and make the degraded that freeze-dried powder can be avoided nicorandil.Therefore, Japan succeeded in developing the injection nicorandil and is at first in Japan going on the market in 1993.But the lyophilizing auxiliary shape agent that is adopted in the injection nicorandil preparation of Japan is sodium citrate and mannitol, its product can only preserved below 10 ℃, is being higher than under 25 ℃ the condition, and the nicorandil degraded is very fast, therefore its holding conditions is comparatively harsh, is unfavorable for product applying clinically.
In December, 2005, the inventor entrusts the Scientific and Technical Information Institute, Shaanxi Province to look into new center the technology used in the present invention has been carried out looking into newly.Look into new point and look into new demand and be: " nicorandil freeze-dried injection excipient chloro acid; But this lyophilized injectable powder injection for intravenous is used." domestic searching document is: " " Chinese science and technology journal data storehouse " 18 class documents such as (tie up general information, 1989 are so far) ", the searching motif speech is: nicorandil, lyophilized injectable powder, aminoacid; External searching system is: " U.S. DIALOG international on-line retrieval system; The SIN data base "; external search file is: " BIOSISPreviews (1996-present) 10 class documents such as (U.S.'s biological abstracts) ", the searching motif speech is: Nicorandil for Injection (injection nicorandil), Amino acids (aminoacid), Excipient (excipient), Freezedrying/freeze dried (lyophilizing), InjectablePowder/Injection Powder (injectable powder).Looking into new result is: there is no the relevant relevant report for preparing nicorandil freeze-drying powder with aminoacid as auxiliary shape agent both at home and abroad in the pertinent literature.
Summary of the invention
The objective of the invention is to, a kind of preparation method of nicorandil freeze-drying powder is provided, this method adopts the amino acids material as nicorandil lyophilizing auxiliary shape agent, prepared nicorandil freeze-drying powder can be in storage below 25 ℃ more than 2 years, nicorandil freeze-drying powder with respect to Japan, easier transportation and storage are more conducive to product applying clinically.
For above-mentioned purpose, the present invention takes following technical solution:
A kind of preparation method of nicorandil freeze-drying powder is characterized in that, adopts to dissolve in the nicorandil freeze-drying powder of weight ratio 0.1%～50.0% in water for injection, and also dissolving in simultaneously has auxiliary shape agent, can obtain nicorandil freeze-drying powder.
Also add at least a in pH regulator agent, antioxidant and the complexing of metal ion agent raw material in the above-mentioned nicorandil freeze-drying powder, method aseptic filtration routinely, fill, lyophilization can obtain nicorandil freeze-drying powder;
Or after dissolving in nicorandil freeze-drying powder in the water for injection, pH value is adjusted to 3.0～9.0, add auxiliary shape agent then, add at least a in pH regulator agent, antioxidant and the complexing of metal ion agent raw material again, method aseptic filtration routinely, fill, lyophilization can obtain nicorandil freeze-drying powder.
The nicorandil freeze-drying powder that adopts this method to make, can delay the degradation speed of nicorandil greatly, improve the stability of injection nicorandil, can preserve more than 2 years in the condition below 25 ℃, reduced the generation of objectionable impurities, improve the quality of products, help to reduce the generation incident of untoward reaction, guaranteed the safety of patient's medication.
The specific embodiment
The present invention is described in further detail below in conjunction with preparation of product production example that the applicant provides.
The present invention investigates two kinds of prescriptions that prepare nicorandil freeze-drying powder of technique scheme, in the prescription of investigating, the content range of nicorandil is 0.1%～50.0% (weight ratio), be lower than 0.1% and be higher than at 50.0% o'clock and still can make stay-in-grade product though be lower than drug content, but do not had in all senses on clinical practice and pharmaceutics, the present invention does not carry out case expedition.
Embodiment 1: the nicorandil consumption is 6.1%, auxiliary shape agent is the preparation of the injection nicorandil of L-serine
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 6.1 | 2 |
| The L-serine | 90.9 | 30 |
| Sodium sulfite | 3.0 | 1 |
| Add up to | 100 | 33 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and make dissolving in right amount, add water for injection to 1000ml, fill, every bottled 1ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 2mg.
Embodiment 2: the nicorandil consumption is 3.8%, auxiliary shape agent is the preparation of the injection nicorandil of L-serine
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 3.8 | 2 |
| The L-serine | 96.2 | 50 |
| Add up to | 100 | 52 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection then to 1000ml, method aseptic filtration routinely, fill, every bottled 1ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 2mg.
Embodiment 3: the nicorandil consumption is 7.4%, auxiliary shape agent is the preparation of the injection nicorandil of L-serine
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 7.4 | 12 |
| The L-serine | 92.6 | 150 |
| Add up to | 100 | 162 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection then to 1000ml, method aseptic filtration routinely, fill, every bottled 1ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 12mg.
Embodiment 4: the nicorandil consumption is 5.6%, auxiliary shape agent is the preparation of the injection nicorandil of L-serine
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 5.6 | 48 |
| The L-serine | 93.8 | 800 |
| Disodium edetate | 0.6 | 4.8 |
| Add up to | 100 | 852.8 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection then to 8000ml, method aseptic filtration routinely, fill, every bottled 8ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 48mg.
Embodiment 5: the nicorandil consumption is 3.8%, auxiliary shape agent is the preparation of the injection nicorandil of glycine
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 3.8 | 12 |
| Glycine | 95.4 | 300 |
| Sodium sulfite | 0.6 | 2 |
| Disodium edetate | 0.2 | 0.6 |
| Add up to | 100 | 314.6 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection to 3000ml, method aseptic filtration routinely, fill, every bottled 3ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 12mg.
Embodiment 6: the nicorandil consumption is 4.7%, auxiliary shape agent is the preparation of the injection nicorandil of glycine
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 4.7 | 5 |
| Glycine | 94.3 | 100 |
| Sodium sulfite | 1.0 | 1 |
| Add up to | 100 | 106 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection to 1000ml, method aseptic filtration routinely, fill, every bottled 1ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 5mg.
Embodiment 7: the nicorandil consumption is 5.7%, auxiliary shape agent is the preparation of the injection nicorandil of glycine
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 5.7 | 12 |
| Glycine | 94.3 | 200 |
| Add up to | 100 | 212 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection to 2000ml, method aseptic filtration routinely, fill, every bottled 2ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 12mg.
Embodiment 8: the nicorandil consumption is 6.0%, auxiliary shape agent is the preparation of the injection nicorandil of glycine
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 6.0 | 48 |
| Glycine | 94.0 | 750 |
| Add up to | 100 | 798 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection to 10000ml, method aseptic filtration routinely, fill, every bottled 10ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 48mg.
Embodiment 9: the nicorandil consumption is 2.0%, auxiliary shape agent is the L-serine: the preparation of the injection nicorandil of glycine (1:1)
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 2.0 | 1 |
| The L-serine | 49.0 | 25 |
| Glycine | 49.0 | 25 |
| Add up to | 100 | 51 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection to 1000ml, method aseptic filtration routinely, fill, every bottled 1ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 1mg.
Embodiment 10: the nicorandil consumption is 6.25%, auxiliary shape agent is the L-serine: the preparation of the injection nicorandil of glycine (1: 2)
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 6.25 | 10 |
| The L-serine | 31.25 | 50 |
| Glycine | 62.5 | 100 |
| Add up to | 100 | 160 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection to 2000ml, method aseptic filtration routinely, fill, every bottled 2ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 10mg.
Embodiment 11: the nicorandil consumption is 1.0%, auxiliary shape agent is the L-serine: the preparation of the injection nicorandil of glycine (3: 1)
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 1.0 | 24 |
| The L-serine | 74.2 | 1800 |
| Glycine | 24.8 | 600 |
| Add up to | 100 | 2424 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and make dissolving in right amount, add water for injection to 24000ml, method aseptic filtration routinely, fill, every bottled 24ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 24mg.
Embodiment 12: the nicorandil consumption is 10.4%, auxiliary shape agent is an alanine: the preparation of the injection nicorandil of phenylalanine (2: 1)
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 10.4 | 12 |
| Alanine | 57.8 | 67 |
| Phenylalanine | 28.4 | 33 |
| Ascorbic acid | 3.4 | 4 |
| Add up to | 100 | 116 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection to 2000ml, method aseptic filtration routinely, fill, every bottled 2ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 12mg.
Embodiment 13: the nicorandil consumption is 8.7%, auxiliary shape agent is the preparation of leucic injection nicorandil
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 8.7 | 48 |
| Leucine | 90.4 | 500 |
| Cyclohexanediamine four sodium acetates | 0.9 | 5 |
| Add up to | 100 | 553 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection to 10000ml, method aseptic filtration routinely, fill, every bottled 10ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 48mg.
Embodiment 14: the nicorandil consumption is 2.0%, auxiliary shape agent is a proline: the preparation of the injection nicorandil of aspartic acid (4: 1)
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 2.0 | 2 |
| Proline | 78.4 | 80 |
| Aspartic acid | 19.6 | 20 |
| Add up to | 100 | 102 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and make dissolving in right amount, add water for injection to 1000ml, method aseptic filtration fill routinely, every bottled 1ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 2mg.
Embodiment 15: the nicorandil consumption is 4.8%, auxiliary shape agent is a glycine: aspartic acid is the preparation of 1: 1 injection nicorandil
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 4.8 | 100 |
| Glycine | 47.6 | 1000 |
| Aspartic acid | 47.6 | 1000 |
| Add up to | 100 | 2100 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and make dissolving in right amount, add water for injection to 25000ml, regulate pH value to 6.5 ± 0.5, method aseptic filtration fill routinely, every bottled 25ml with the 0.1mol/L sodium hydroxide solution, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 100mg.
The injection Buddhist nun that embodiment 16 principal agent consumptions are 0.65%, auxiliary shape agent is glutamic acid is with can your preparation of ground
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 0.65 | 1 |
| Glutamic acid | 98.7 | 150 |
| Diethyl triamine six acetic acid | 0.65 | 1 |
| Add up to | 100 | 152 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and make dissolving in right amount, add water for injection, regulate pH value to 6.5 ± 0.5 with the 0.1mol/L sodium hydroxide solution to 1000ml, method aseptic filtration routinely, fill, every bottled 1ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 1mg.
Embodiment 17: the nicorandil consumption is 20.5%, auxiliary shape agent is the preparation of the injection nicorandil of Fu's propylhomoserin
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 20.5 | 100 |
| Fu's propylhomoserin | 76.9 | 375 |
| Sodium pyrosulfite | 2.6 | 12.5 |
| Add up to | 100 | 487.5 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection, regulate pH value to 6.5 ± 0.5 with the 0.1mol/L hydrochloric acid solution to 12500ml, method aseptic filtration routinely, fill, every bottled 12.5ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 100mg.
Embodiment 18: the nicorandil consumption is 6.7%, auxiliary shape agent is a valine: isoleucine: glutamic acid is the preparation of 5: 5: 1 injection nicorandil
Prescription:
| Title | Content (%) | 1000 bottles of inventorys (g) |
| Nicorandil | 6.7 | 12 |
| Valine | 42.4 | 75 |
| Isoleucine | 42.4 | 75 |
| Glutamic acid | 8.5 | 15 |
| Add up to | 100 | 177 |
Method for making: take by weighing each composition by recipe quantity, add the injection water and dissolve in right amount, add water for injection to 2000ml, conventional method aseptic filtration, fill, every bottled 2ml, lid is rolled in lyophilization, promptly.Every bottle contains nicorandil 12mg.
The foregoing description can also be enumerated many, as space is limited, enumerates no longer one by one, but as long as in the scope of technical scheme of the present invention, all can reach purpose of the present invention.
The nicorandil freeze-drying powder that the applicant makes the foregoing description, can preserve more than 2 years in the condition below 25 ℃, the experiment proved that, the nicorandil freeze-drying powder of this method preparation can delay the degradation speed of nicorandil greatly, improve the stability of injection nicorandil, reduced the generation of objectionable impurities, improve the quality of products, help to reduce the generation incident of untoward reaction, guaranteed the safety of patient's medication.
Table adopts the injection nicorandil of the inventive method production and the stability of the injection nicorandil that other method is produced to compare
| Experimental condition | The inventive method: embodiment 3 (prescription: every bottle contains nicorandil 12mg, L-serine 150mg) | Other method (prescription: every bottle contains nicorandil 12mg, mannitol 150mg) |
| 40 ℃, RH=75% were placed 10 days | Content drops to 98.8% from 102.3% | Content drops to 89.7% from 101.1% |
| Around 40 ℃, RH=75% are placed | Content drops to 88.8% from 102.3% | Content drops to 69.3% from 101.1% |
| 30 ℃, RH=75% were placed 6 months | Content drops to 95.7% from 102.3% | Content drops to 57.8% from 101.1% |
| Room temperature, RH=40～75% were placed 2 years | Content drops to 94.6% from 102.3% | Content drops to 76.5% from 101.1% |
Claims (8)
1. the preparation method of a nicorandil freeze-drying powder is characterized in that, adopts to dissolve in the nicorandil of weight ratio 0.1%～50.0% in water for injection, also dissolving in simultaneously has auxiliary shape agent, method aseptic filtration routinely, fill, lyophilization can obtain nicorandil freeze-drying powder.
2. the preparation method of a nicorandil freeze-drying powder, it is characterized in that, the nicorandil of weight ratio 0.1%～50.0% is dissolved in employing in water for injection, also dissolve in simultaneously auxiliary shape agent is arranged, and add the wherein a kind of or whole of antioxidant, complexing of metal ion agent, method aseptic filtration routinely, fill, lyophilization can obtain nicorandil freeze-drying powder.
3. the preparation method of a nicorandil freeze-drying powder, it is characterized in that, the nicorandil of weight ratio 0.1%～50.0% is dissolved in employing in water for injection, also dissolve in simultaneously auxiliary shape agent is arranged, with the pH value regulator solution pH value is adjusted to 3.0～9.0 then, method aseptic filtration routinely, fill, lyophilization can obtain nicorandil freeze-drying powder.
4. the preparation method of a nicorandil freeze-drying powder, it is characterized in that, the nicorandil of weight ratio 0.1%～50.0% is dissolved in employing in water for injection, also dissolving in simultaneously has auxiliary shape agent, and add antioxidant, complexing of metal ion agent wherein a kind of or whole, with the pH value regulator solution pH value is adjusted to 3.0～9.0 then, method aseptic filtration routinely, fill, lyophilization can obtain nicorandil freeze-drying powder.
5. as one of them described method of claim 1～4, it is characterized in that, said auxiliary shape agent is the amino acids material, comprise one or more mixing uses wherein of serine, glycine, alanine, valine, leucine, isoleucine, aspartic acid, glutamic acid, lysine, arginine, tyrosine, cysteine, its weight ratio is 50%～99.9%.
6. as claim 3 or 4 described methods, it is characterized in that, said pH regulator agent comprises one or more mixing uses wherein of hydrochloric acid, sodium hydroxide, tartaric acid, sodium tartrate, citric acid, sodium citrate, disodium citrate, citric acid trisodium, sodium carbonate, sodium bicarbonate, phosphoric acid, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, and its consumption gets final product for the medicinal liquid pH value is transferred to 3.0～9.0.
7. as claim 2 or 4 described methods, it is characterized in that, said antioxidant selects one or more mixing in sodium sulfite, sodium pyrosulfite, sodium sulfite, sodium thiosulfate, thiourea, ascorbic acid, vitamin E or the pharmaceutical production antioxidant commonly used to use, and its weight ratio is 0～10%.
8. as claim 2 or 4 described methods, it is characterized in that, said complexing of metal ion agent selects one or more mixing of disodium edetate, cyclohexanediamine four sodium acetates, N-hydroxy-ethylenediamine three acetic acid, diethyl triamine six acetic acid to use, and its weight ratio is 0～5%.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2006100417782A CN100417381C (en) | 2006-02-09 | 2006-02-09 | Nicorandil freeze-drying powder preparation method |
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|---|---|---|---|
| CNB2006100417782A CN100417381C (en) | 2006-02-09 | 2006-02-09 | Nicorandil freeze-drying powder preparation method |
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| CN1839837A true CN1839837A (en) | 2006-10-04 |
| CN100417381C CN100417381C (en) | 2008-09-10 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101474161B (en) * | 2009-01-14 | 2011-11-16 | 北京四环科宝制药有限公司 | Nicorandil freeze-dried injection and preparation method thereof |
| CN110123749A (en) * | 2019-06-03 | 2019-08-16 | 北京普瑞博思投资有限公司 | Nicorandil fat micro sphere preparation and preparation method thereof |
| CN114557983A (en) * | 2022-03-18 | 2022-05-31 | 北京诺和德美医药科技有限公司 | Stable bromhexine hydrochloride solution for inhalation and preparation method thereof |
| CN115381825A (en) * | 2022-08-31 | 2022-11-25 | 北京诺康达医药科技股份有限公司 | Nicorandil pharmaceutical composition and preparation method thereof |
| CN115624527A (en) * | 2022-09-20 | 2023-01-20 | 朗天药业(湖北)有限公司 | Nicorandil freeze-dried powder injection and preparation method and application thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0653658B2 (en) * | 1984-12-17 | 1994-07-20 | 中外製薬株式会社 | Stable tablet manufacturing method |
| KR950010150B1 (en) * | 1986-01-14 | 1995-09-11 | 쥬우가이세이야꾸 가부시끼가이샤 | Method of the stabilization of nicorandil injection |
| JP2001187735A (en) * | 2000-01-05 | 2001-07-10 | Towa Yakuhin Kk | Method for production of stable nicorandil-containing powder |
-
2006
- 2006-02-09 CN CNB2006100417782A patent/CN100417381C/en active Active
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101474161B (en) * | 2009-01-14 | 2011-11-16 | 北京四环科宝制药有限公司 | Nicorandil freeze-dried injection and preparation method thereof |
| CN110123749A (en) * | 2019-06-03 | 2019-08-16 | 北京普瑞博思投资有限公司 | Nicorandil fat micro sphere preparation and preparation method thereof |
| CN110123749B (en) * | 2019-06-03 | 2022-01-25 | 太阳升(亳州)生物医药科技有限公司 | Nicorandil lipid microsphere preparation and preparation method thereof |
| CN114557983A (en) * | 2022-03-18 | 2022-05-31 | 北京诺和德美医药科技有限公司 | Stable bromhexine hydrochloride solution for inhalation and preparation method thereof |
| CN114557983B (en) * | 2022-03-18 | 2022-12-27 | 北京诺和德美医药科技有限公司 | Stable bromhexine hydrochloride solution for inhalation and preparation method thereof |
| CN115381825A (en) * | 2022-08-31 | 2022-11-25 | 北京诺康达医药科技股份有限公司 | Nicorandil pharmaceutical composition and preparation method thereof |
| CN115381825B (en) * | 2022-08-31 | 2024-07-05 | 北京诺康达医药科技股份有限公司 | Nicotil pharmaceutical composition and preparation method thereof |
| CN115624527A (en) * | 2022-09-20 | 2023-01-20 | 朗天药业(湖北)有限公司 | Nicorandil freeze-dried powder injection and preparation method and application thereof |
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| Publication number | Publication date |
|---|---|
| CN100417381C (en) | 2008-09-10 |
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